ADRENAL GLAND

Anatomy and Physiology

The adrenal gland consists of the cortex and the medulla. The adrenal medulla is made of chromaffin cells that secrete norepinephrine and epinephrine in response to fear, anger, or stress. These hormones result in increased heart rate, raised blood pressure, vasoconstriction, and altered carbohydrate metabolism. The adrenal cortex is further divided into three zones that secrete five groups of steroids: corticosteroids, aldosterone, androgens, estrogens, and progesterone. All are derived from cholesterol. The outer region, the zona glomerulosa, secretes the main mineralocorticoid, aldosterone. Most of the glucocorticoids, androgens, and progesterone are secreted by cells in the middle, the zona fasciculata. The inner zona reticularis is responsible for the remainder of the steroids secreted by the cortex. This area atrophies in older males and enlarges with pregnancy and in the summer in women of childbearing age. Unlike the medulla, removal of the cortex is incompatible with life. The glucocorticoids are bound to transcortin, carrying 70% of the circulating cortisol.

Aldosterone secretion, the serum potassium level, and ACTH are controlled mainly by angiotensin II. It acts on the collecting duct of the kidney, the salivary glands, and the gut mucosa, causing the excretion of hydrogen and potassium ions in exchange for sodium ions.

Dysfunction

Hyperadrenocorticism

Hyperadrenocorticism causes Cushing’s syndrome, characterized by centripetal obesity with moon facies and buffalo hump, hirsutism, easy bruisability, amenorrhea, manic behavior or psychosis, osteopenia, muscle weakness, and violaceous striae of the abdomen, hips, and breasts. Excess of glucocorticoids leads to increased volume and blood pressure, hypokalemia, negative nitrogen balance, and glucose intolerance because they are insulin antagonists. The causes include pharmacologic administration of glucocorticoids or ACTH and pathologic conditions, such as an ACTH-producing pituitary adenoma, adrenal hyperplasia, adrenal adenomas or carcinomas, or secondary ectopic ACTH production in some lung, thymus, or pancreatic tumors. Presentation of ectopic ACTH production may be atypical, including hyperpigmentation due to the stronger melanocyte-stimulating hormonelike properties. Cushing’s syndrome usually presents in the third to sixth decade of life and occurs more commonly in women. At surgical exploration, 75% to 90% of these cases are due to corticotropic cell adenomas with autonomous secretion and are therefore not under hypothalamic control. In the other 10% to 25%, no pituitary tumor is found.

Adrenocortical Insufficiency

Primary adrenocortical insufficiency (i.e., Addison’s disease) may be due to destruction of the gland from autoimmune disease, tumors, infection, hemorrhage, or metabolic failure in hormone production. Secondary causes are hypopituitarism or suppression by exogenous steroids, ACTH (e.g., autonomous tumors), or endogenous steroids. The disease is characterized by fatigability, weakness, anorexia, nausea and vomiting, weight loss, hyperpigmentation, hypotension, and occasionally hypoglycemia. In women, the loss of adrenal androgens causes a loss of axillary and pubic hair. The absence of glucocorticoid causes volume depletion with decreased cardiac output and function, leading to shock that is sometimes called addisonian crisis.

Overproduction of Aldosterone

Primary overproduction of aldosterone is due to an adenoma (i.e., Conn’s syndrome) or nodular hyperplasia of the zona glomerulosa and is associated with moderate hypertension, hypokalemia, alkalosis, and normal or slightly increased sodium levels. Symptoms include muscle weakness, nocturnal polyuria, and cramping of the hands. Secondary excess is seen in cirrhosis, ascites, the nephrotic syndrome, and with diuretic use if the patient is volume depleted. In primary overproduction, tests show elevated aldosterone levels with severely suppressed plasma renin levels that do not respond to volume depletion; in secondary overproduction, one finds renin levels that are not suppressed and that may rise using various methods. Congenital or infantile forms of hypoaldosteronism are due to an enzyme defect in production. In the elderly, the condition is thought to be caused by an intrinsic renal problem, causing inadequate renin production. Many patients are diabetic and present with moderate renal insufficiency and serum potassium levels that are much higher than expected.